Excitatory and inhibitory actions of isoflurane in bovine chromaffin cells.
Excitatory and inhibitory actions of isoflurane in bovine chromaffin cells.
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DOI：
10.1152/jn.00571.2006
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发表时间：
2006-12
影响因子：
2.5
通讯作者：
Zheng Xie;B. E. Herring;A. P. Fox
中科院分区：
文献类型：
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作者：
Zheng Xie;B. E. Herring;A. P. Fox
异氟醚，一种卤化挥发性麻醉剂，被认为是通过抑制中枢神经系统功能来产生麻醉的。许多麻醉剂，包括异氟醚，被认为可以调节和/或直接激活GABA(A)受体。已知染色质细胞表达功能性GABA(A)受体。我们之前的研究表明，GABA(A)受体的激活，使用特异性激动剂，导致由去极化阴离子平衡电位引起的细胞兴奋。在这项研究中，我们的目标是确定异氟醚是否模仿这种反应，并探索这种激活的功能后果。此外，我们试图研究异氟醚对烟碱乙酰胆碱受体（nachr）的作用，因为它们介导这些细胞中的“交感驱动”。在这些研究中，Ca（2+）指示剂fura-2被用来测定[Ca(2+)](i)。用安培法测定儿茶酚胺释放量。我们发现牛肾上腺嗜铬细胞被临床相关浓度的异氟醚激发。异氟醚直接激活染色质细胞中的GABA(A)受体，使细胞去极化并升高[Ca(2+)](i)。异氟醚直接作用于嗜铬细胞可引起嗜铬细胞分泌儿茶酚胺。与此同时，异氟醚抑制了nachr的激活，这可能会阻止对染色质细胞的“交感驱动”。后一种结果可能有助于解释为什么异氟醚会产生临床观察到的低血压。
Isoflurane, a halogenated volatile anesthetic, is thought to produce anesthesia by depressing CNS function. Many anesthetics, including isoflurane, are thought to modulate and/or directly activate GABA(A) receptors. Chromaffin cells are known to express functional GABA(A) receptors. We previously showed that activation of the GABA(A) receptors, with specific agonists, leads to cellular excitation resulting from the depolarized anion equilibrium potential. In this study, our goal was to determine whether isoflurane mimicked this response and to explore the functional consequences of this activation. Furthermore, we sought to study the actions of isoflurane on nicotinic acetylcholine receptors (nAChRs) as they mediate the "sympathetic drive" in these cells. For these studies the Ca(2+)-indicator dye fura-2 was used to assay [Ca(2+)](i). Amperometric measurements were used to assay catecholamine release. We show that bovine adrenal chromaffin cells were excited by isoflurane at clinically relevant concentrations. Isoflurane directly activated GABA(A) receptors found in chromaffin cells, which depolarized the cells and elevated [Ca(2+)](i). Application of isoflurane directly to the chromaffin cells elicited catecholamine secretion from these cells. At the same time, isoflurane suppressed activation of nAChRs, which presumably blocks "sympathetic drive" to the chromaffin cells. These latter results may help explain why isoflurane produces the hypotension observed clinically.